Immunity to infection by the intracellular parasitic Leishmania is mediated by sensitized T cells; however, the antigens which they recognize are still poorly defined. We have previously shown that the cell-mediated response of individuals with healed or healing forms of cutaneous leishmaniasis occurs to as many as 50-70 distinct antigens; however, it is unclear whether all the antigens capable of inducing a T cell response are important in protective immunity. As this question can only be addressed using purified distinct antigens directly in vaccine studies, and as these are most conveniently obtained through molecular cloning, we have begun to examine the T-cell immunogenicity of recombinant leishmanial antigens initially selected on the basis of their reactivity with human kala-azar serum. Although this approach relies upon overlap of T- and B-cell epitopes, a significant proportion of recombinants so selected showed immunogenicity in initial human T-cell proliferation assays. Work is presently underway to purify these putative T-cell antigens for further characterization. Investigation of the T cell response of leishmania patients to soluble antigen pulsed monocytes or monocytes infected with amastigotes has demonstrated the fundamental role of the CD4 subset of T cells in mounting both a proliferative and gamma interferon response to both sources of antigen. The role of CD8 cells in these responses varies between patients and the pattern of CD8 mediated response does not correlate with the source of antigen, i.e., endogenous (infected monocyte) or exogenous (antigen pulsed monocyte). Although no correlation was found between CD8 responses and live antigen, the use of live antigen to prestimulate patient cells has illustrated and enhanced gamma interferon response by mucocutaneous patient T cells when compared to cells from cutaneous patients.